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Genetic changes in ATM and ATR/CHEK1 as prognostic indicators in cancer

a gene and atr/chek1 technology, applied in the field of gene changes in atm and atr/chek1 as prognostic indicators in cancer, can solve the problems of head and neck tumor development, chromosomal instability is a relatively large number, and achieve the effect of equal survival

Active Publication Date: 2012-09-11
UNIVERSITY OF PITTSBURGH
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Problems solved by technology

Chromosomal segregational defects, involving multipolar spindles are a common cause of numerical chromosomal instability in OSCC (SAUNDERS et al.
Thus, chromosomal instability is a relatively early event in head and neck tumor development.
Thus, perturbation of either ATM or ATR may have a ripple effect and affect the regulation and control of numerous proteins and pathways involved in the DNA damage response.

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  • Genetic changes in ATM and ATR/CHEK1 as prognostic indicators in cancer
  • Genetic changes in ATM and ATR/CHEK1 as prognostic indicators in cancer
  • Genetic changes in ATM and ATR/CHEK1 as prognostic indicators in cancer

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Embodiment Construction

[0055]For clarity of description, and not by way of limitation, the present invention is divided into the following subsections:[0056](i) methods of identifying 11q deletion;[0057](ii) methods of identifying ATR / CHEK1 / CCND1 copy number alterations and / or overexpression;[0058](iii) methods of identifying target patients;[0059](iv) methods of treating target patients; and[0060](v) kits.

5.1 Methods of Identifying 11q Deletion

[0061]In one non-limiting aspect of the invention, the present invention provides for identifying an 11q deletion in a patient sample.

[0062]The term “11q deletion” refers to a deletion in the long arm of human chromosome 11 which comprises at least a part of the ATM gene and may further comprise at least a portion of MRE11A, H2AFX, and / or CHEK1.

[0063]A patient sample is a sample that contains genomic material. For example, but not by way of limitation, the sample may be a cell, a tissue, or DNA. In a specific, non-limiting embodiment, the sample comprises a cancer ...

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Abstract

The present invention relates to the discovery that, in human cancer, an 11q deletion of ATM together with an increase in ATR and CHEK1 expression correlates with resistance to ionizing radiation which could be overcome by inhibition of the ATR / CHEK1 pathway. It provides for methods of identifying patients unlikely to exhibit an adequate response to radiation therapy and / or chemotherapy who may benefit from ATR / CHEK1 pathway inhibition, as well as methods of treating said patients.

Description

PRIORITY CLAIM[0001]This application claims priority to U.S. Provisional Application No. 60 / 908,891, filed Mar. 29, 2007; U.S. Provisional Application No. 60 / 912,086, filed Apr. 16, 2007; and U.S. Provisional Application No. 60 / 912,355, filed Apr. 17, 2007, the contents of each of which are incorporated by reference in their entireties herein.GRANT INFORMATION[0002]The subject matter of the present invention was developed, at least in part, under National Institutes of Health Grant No. RO1DE14729, P30CA47904, RO1DE016086, R25CA089507 and P50CA097190, so that the United States Government has certain rights herein.1. INTRODUCTION[0003]The present invention relates to the discovery that, in human cancer, an 11q deletion of ATM together with an increase in ATR and CHEK1 expression correlates with resistance to ionizing radiation which could be overcome by inhibition of the ATR / CHEK1 pathway. It provides for methods of identifying patients unlikely to exhibit an adequate response to radi...

Claims

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Application Information

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Patent Type & Authority Patents(United States)
IPC IPC(8): C12Q1/68
CPCG01N33/5091C12Q1/6886G01N33/57484A61P35/00A61P35/04
Inventor GOLLIN, SUSANNE M.PARIKH, RAHUL ATULHUANG, XIN
Owner UNIVERSITY OF PITTSBURGH
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